Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3J8P0B)

• DOT Name: pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3)
• Synonyms: EC 2.1.1.-; Protein ftsJ homolog 3; Putative rRNA methyltransferase 3
• Gene Name: FTSJ3
• Related Disease:
  Hyperglycemia
  Obesity
  Streptococcal B infection
• UniProt ID: SPB1_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY; 8IR1
• EC Number: 2.1.1.-
• Pfam ID: PF11861 ; PF01728 ; PF07780
• Sequence:
  MGKKGKVGKSRRDKFYHLAKETGYRSRSAFKLIQLNRRFQFLQKARALLDLCAAPGGWLQ
  VAAKFMPVSSLIVGVDLVPIKPLPNVVTLQQDITTERCRQALRKELKTWKVDVVLNDGAP
  NVGASWVHDAYSQAHLTLMALRLACDFLARGGSFITKVFRSRDYQPLLWIFQQLFRRVQA
  TKPQASRHESAEIFVVCQGFLAPDKVDSKFFDPKFAFKEVEVQAKTVTELVTKKKPKAEG
  YAEGDLTLYHRTSVTDFLRAANPVDFLSKASEIMVDDEELAQHPATTEDIRVCCQDIRVL
  GRKELRSLLNWRTKLRRYVAKKLKEQAKALDISLSSGEEDEGDEEDSTAGTTKQPSKEEE
  EEEEEEQLNQTLAEMKAQEVAELKRKKKKLLREQRKQRERVELKMDLPGVSIADEGETGM
  FSLSTIRGHQLLEEVTQGDMSAADTFLSDLPRDDIYVSDVEDDGDDTSLDSDLDPEELAG
  VRGHQGLRDQKRMRLTEVQDDKEEEEEENPLLVPLEEKAVLQEEQANLWFSKGSFAGIED
  DADEALEISQAQLLFENRRKGRQQQQKQQLPQTPPSCLKTEIMSPLYQDEAPKGTEASSG
  TEAATGLEGEEKDGISDSDSSTSSEEEESWEPLRGKKRSRGPKSDDDGFEIVPIEDPAKH
  RILDPEGLALGAVIASSKKAKRDLIDNSFNRYTFNEDEGELPEWFVQEEKQHRIRQLPVG
  KKEVEHYRKRWREINARPIKKVAEAKARKKRRMLKRLEQTRKKAEAVVNTVDISEREKVA
  QLRSLYKKAGLGKEKRHVTYVVAKKGVGRKVRRPAGVRGHFKVVDSRMKKDQRAQQRKEQ
  KKKHKRK
• Function: RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation; (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2'-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system. RNA 2'-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5. Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine. Recruited to HIV-1 RNA via interaction with TARBP2/TRBP.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[1]
Obesity	DIS47Y1K	Limited	Biomarker	[1]
Streptococcal B infection	DISN80QT	Limited	Biomarker	[2]

6 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[5]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (FTSJ3).	[8]

References

• [1] Evaluation of Bacillus subtilis SPB1 biosurfactant effects on hyperglycemia, angiotensin I-converting enzyme (ACE) activity and kidney function in rats fed on high-fat-high-fructose diet.Arch Physiol Biochem. 2017 May;123(2):112-120. doi: 10.1080/13813455.2016.1261902. Epub 2016 Dec 25.
• [2] Subtractive hybridization identifies a novel predicted protein mediating epithelial cell invasion by virulent serotype III group B Streptococcus agalactiae.Infect Immun. 2003 Dec;71(12):6857-63. doi: 10.1128/IAI.71.12.6857-6863.2003.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [8] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.